title: (13)C-uracil breath test to predict 5-fluorouracil toxicity in gastrointestinal cancer patients.
abstract: OBJECTIVE
  Up to 30 % of patients undergoing 5-fluorouracil (5FU)-based chemotherapy experience severe toxicity. Dihydropyrimidine dehydrogenase (DPD) deficiency explains 36-61 % of cases. Predicting toxicity is an unmet challenge. Uracil breath test (UraBT) consists of measuring (13)CO2 in exhaled breath after ingestion of 2-(13)C-uracil to evaluate pyrimidine (and 5FU) catabolism.
  
  
  METHODS
  We studied 33 gastrointestinal cancer patients previously exposed to 5FU: Thirteen had grade 3-4 and 20, grade 0-1 toxicity. The following tests were used to evaluate pyrimidine catabolism: (1) sequencing of three exons of DPYD; (2) plasma dihydrouracil/uracil ratio (UH2/U); and (3) UraBT. We tested the performance of UraBT to discriminate patients who had grade 0-1 toxicity versus grade 3-4 toxicity and patients with and without proven DPD deficiency.
  
  
  RESULTS
  Of the thirteen patients, four grade 3-4 toxicity patients were proved to be DPD-deficient: Three had deleterious mutations (IVS14 + 1G>A in one; single nucleotide polymorphism 2846A>T in two), and one had low UH2/U ratio. Mean delta over baseline in 50 min (DOB50) significantly differed between groups. DOB50≤161.4 discriminated individuals with grade 3-4 versus grade 0-1 toxicity (sensitivity = 61.5 %; specificity = 85 %) and DPD-deficient versus non-DPD-deficient (sensitivity = 75 %; specificity = 85 %).
  
  
  CONCLUSIONS
  UraBT has moderate accuracy in discriminating individuals who manifested severe toxicity from those who had mild or no toxicity to 5FU.
authors.affiliation: Instituto Alfa de Gastroenterologia, Hospital das Clínicas da Universidade Federal de Minas Gerais, Av. Professor Alfredo Balena, 110, Belo Horizonte, MG, 30130-100, Brazil, geraldo.onco@gmail.com.
authors.forename: Geraldo Felício
authors.initials: GF
authors.lastname: Cunha-Junior
authors.forename: Luiz
authors.initials: L
authors.lastname: De Marco
authors.forename: Luciana
authors.initials: L
authors.lastname: Bastos-Rodrigues
authors.forename: Marina Borges
authors.initials: MB
authors.lastname: Bolina
authors.forename: Flavia Linhares
authors.initials: FL
authors.lastname: Martins
authors.forename: Gerson Antonio
authors.initials: GA
authors.lastname: Pianetti
authors.forename: Isabela Costa
authors.initials: IC
authors.lastname: Cesar
authors.forename: Luiz Gonzaga
authors.initials: LG
authors.lastname: Coelho
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D001944:Breath Tests / Q000379:methods; D002247:Carbon Isotopes; D054067:Dihydropyrimidine Dehydrogenase Deficiency / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects* / Q000627:therapeutic use; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D014498:Uracil
chemical_list: D000964:Antimetabolites, Antineoplastic; D002247:Carbon Isotopes; D014498:Uracil; D005472:Fluorouracil